Successful treatment of immune-related cystitis with bladder hydrodistension.

Introduction: Although immune checkpoint inhibitors offer significant therapeutic benefits to patients with advanced cancer, they can also cause a variety of immune-related adverse events. As immune checkpoint inhibitors are being widely used, rare immune-related adverse events are being reported. Case presentation: A 70-year-old man with advanced salivary duct carcinoma was treated with pembrolizumab following radiotherapy. After receiving two doses of pembrolizumab, the patient experienced symptoms such as micturition pain and hematuria. Immune-related cystitis was suspected, and the patient underwent a bladder biopsy and bladder hydrodistension. Histological analysis revealed non-neoplastic bladder mucosa with CD8-positive lymphocyte-dominant inflammatory cell infiltration, consistent with immune-related cystitis. The patient's bladder symptoms improved postoperatively without steroid administration. Conclusion: Although steroids are commonly administered to treat immune-related adverse events, bladder hydrodistension may be a promising treatment option for immune-related cystitis to avoid administration of steroids, which may impair the therapeutic effect of immune checkpoint inhibitors.

Sarcomatoid urothelial carcinoma of the renal pelvis treated with immunotherapy.

BACKGROUND: Sarcomatoid carcinoma is a rare, high-grade malignancy with epithelial and mesenchymal components. It may be a good candidate for immunotherapy because it is associated with overexpression of programmed cell death ligand 1. Sarcomatoid urothelial carcinoma (UC) of the upper urinary tract is extremely rare. Here we report the first case of sarcomatoid UC of the renal pelvis that responded to immunotherapy. CASE PRESENTATION: A 79-year-old man was referred to our hospital complaining of various symptoms, including anorexia and abdominal pain. A computed tomography scan revealed a right atrial tumor, a 9 cm left renal mass with a renal vein tumor thrombus, para-aortic lymphadenopathy, and multiple small lung nodules. The patient underwent resection of the right atrial tumor. Pathological analysis of the tumor did not lead to an accurate diagnosis even after several rounds of immunohistochemistry. He underwent a needle biopsy of the left kidney and was initially diagnosed with collecting duct carcinoma, a rare subtype of renal cell carcinoma (RCC). Following the initial diagnosis, immunotherapy with nivolumab and ipilimumab commenced. Thereafter, almost all lesions, including the left renal tumor, were reduced in size. However, he underwent a left nephrectomy approximately a year after beginning immunotherapy due to repeated left renal bleeding. Histological examination of the nephrectomy specimen revealed two forms of cancer-sarcomatoid UC and conventional high-grade UC. Two months after surgery, the patient was found to have new lung metastases. He underwent chemotherapy with gemcitabine and cisplatin, followed by immunotherapy with pembrolizumab. However, both treatments were ineffective. The patient died of cancer 19 months after his first admission. CONCLUSIONS: The presented case of sarcomatoid UC of the renal pelvis that partially responded to immunotherapy suggests that immunotherapy can be a promising treatment for sarcomatoid UC.

A 40-year-old man with a rapidly growing intrascrotal tumor in the fibroma-thecoma group.

Introduction: Tumors in the fibroma-thecoma group are benign tumors, typically found in the ovaries of postmenopausal women and occasionally develop in the testes. These tumors are mostly treated with radical orchiectomy because preoperative diagnosis confirming the benign nature is difficult. Case presentation: A 40-year-old man was incidentally pointed out to have a right intrascrotal mass, measuring approximately 10 cm on computed tomography. Malignant testicular tumor was suspected based on the location and size of the tumor. The patient underwent right radical orchiectomy. Histologically, the tumor had no evidence of malignancy, and the diagnosis of tumors in the fibroma-thecoma group was made. The patient had no recurrence 8 months after surgery. Conclusion: Intrascrotal tumors in the fibroma-thecoma group are rare benign tumors and mostly treated with radical orchiectomy due to concerns about malignancies. Further investigation is needed for accurate preoperative diagnosis, and we should be aware of these rare tumors.

Mortality risks of body mass index and energy intake trajectories in institutionalized elderly people: a retrospective cohort study.

BACKGROUND: Many factors can identify the mortality risks of institutionalized elderly people; among all such factors, body mass index (BMI) and energy intake (EI) can be employed as independent predictors. The objective of this study was to elucidate about the mortality risks and the trajectory of two parameters obtained from continuously monitored data. METHODS: This retrospective cohort study targeted 218 elderly people who were admitted to a nursing home for at least 6 months between 2007 and 2020 and passed away at the nursing home. BMI and EI (kcal) per body weight (BW) were continuously measured until death. RESULTS: BMI continued to decrease for 5 years until death. The rate of change of BMI significantly increased for 3 years before death (P = 0.004). In contrast, the rate of change of EI per BW significantly increased after 1 year before death (P < 0.001); in addition, 2 months before death, this rate of change significantly exceeded that of BMI (P = 0.007). In the four risk groups that were examined, a BMI of <18.0 + EI per BW of <29.2 and a BMI of <17.3 + EI per BW of <28.3 were significantly correlated with a high risk of death (log-rank test: P < 0.001, P = 0.002, respectively). There was no significant difference in the hazard ratio based on the age at the time of admission; however, when EI per BW was <23.8, the risk of death was significantly higher [hazard ratio = 4.36; 95% confidence interval: 2.31-8.24]. CONCLUSIONS: Elderly people in the current study presented a tendency toward decreasing BMI starting 60 months prior to death even if EI per BW remained constant. In the 1 year before death, EI per BW rapidly decreased. When the rate of change of EI per BW exceeded the rate of decrease of BMI, it was considered to be the point of no return when death was imminent. Our study showed that identifying mortality risks from the relationship between the trajectories of the two parameters that were continuously measured for several months to years is possible.

Changes in Body Mass Index, Energy Intake, and Fluid Intake over 60 Months Premortem as Prognostic Factors in Frail Elderly: A Post-Death Longitudinal Study.

Survival prediction is considered difficult in elderly individuals with cognitive frailty or dementia that leads to death. The aim of this study was to verify temporal changes in body mass index (BMI), energy intake, and fluid intake measured continuously in frail elderly people as prognostic factors for death. We assessed 106 frail elderly individuals who received >2-year care at an elderly care facility and died at the facility. We analyzed temporal changes in BMI, energy intake, and fluid intake from a maximum of 60 months premortem to death and determined the relationship between these parameters. BMI was significantly below the reference values from 9 months prior to death, but energy intake remained constant from 2 months prior to death to death (p < 0.001). However, the mean fluid intake decreased suddenly immediately prior to death. We compared the changes in each parameter during the year prior to death and during the preceding year and found significant differences in all parameters (p < 0.001). From 60 months prior to death to death, BMI, energy intake, and fluid intake decreased in the same order over time. Therefore, these parameters can be used as prognostic factors for death in frail elderly people.

PFC Blood Oxygenation Changes in Four Different Cognitive Tasks.

Aging often results in a decline in cognitive function, related to alterations in the prefrontal cortex (PFC) activation. Maintenance of this function in an aging society is an important issue. Some practices/drills, moderate exercise, mastication, and a cognitive task itself could enhance cognitive function. In this validation study, before evaluating the effects of some drills on the elderly, we examined the neural substrate of blood oxygenation changes by the use of four cognitive tasks and fNIRS. Seven healthy volunteers (mean age 25.3 years) participated in this study. Each task session was designed in a block manner; 4 periods of rests (30 s) and 3 blocks of four tasks (30 s). The tasks used were: a computerized Stroop test, a Wisconsin Card Sorting Test, a Sternberg working memory paradigm, and a semantic verbal fluency task. The findings of the study are that all four tasks activated PFC to some extent, without laterality except for the verbal fluency task. The results confirm that NIRS is suitable for measurement of blood oxygenation changes in frontal brain areas that are associated with all four cognitive tasks.

Influence of Pleasant and Unpleasant Auditory Stimuli on Cerebral Blood Flow and Physiological Changes in Normal Subjects.

The prefrontal cortex (PFC) plays an important role in emotion and emotional regulation. The valence asymmetry hypothesis, proposes that the left/right asymmetry of the PFC activity is correlated with specific emotional responses to stressors. However, this hypothesis still seems to leave room for clarifying neurophysiological mechanisms. The purpose of the present study was to investigate the effects of stimuli with positive and negative valence sounds (hereafter PS, NS) selected from the International Affective Digitized Sounds-2 on physiological and physiological responses, including PFC activity in normal participants. We studied the effect of both stimuli using 12 normal subjects (mean age 26.8 years) on cerebral blood oxygenation in the bilateral PFC by a multi-channel NIRS, alpha wave appearance rate in theta, alpha, beta by EEG, autonomic nervous function by heart rate, and emotional conditions by the State-Trait Anxiety Inventory (STAI) and the visual analogue scale (VAS). PS was selected over 7.00 and NS were fewer than 3.00 in the Pleasure values. Sounds were recorded during 3 s and reproduced at random using software. Every task session was designed in a block manner: seven rests with Brown Noise (30 s) and six tasks (30 s) blocks. All participants performed each session in random order with eyes closed. A paired Student's t-test was used for comparisons (P<0.05). PFC activity showed increases bilaterally during both stimuli with a greater activation of the left side in PS and a tendency of more activation by NS in the right PFC. Significantly greater alpha wave intensity was obtained in PS. Heart rate tended to show smaller values in PS. The STAI level tended to show smaller values in PS, and a significantly greater VAS score was obtained in PS which indicated 'pleasant'. Despite the limitations of this study such as the low numbers of the subjects, the present study indicated that PS provided pleasant psychological and physiological responses and NS unpleasant responses. The PFC was activated bilaterally, implying a valence effect with the possibility of a dominant side.

Relationships Between Gum-Chewing and Stress.

Studies have shown that chewing is thought to affect stress modification in humans. Also, studies in animals have demonstrated that active chewing of a wooden stick during immobilization stress ameliorates the stress-impaired synaptic plasticity and prevents stress-induced noradrenaline release in the amygdala. On the other hand, studies have suggested that the right prefrontal cortex (PFC) dominates the regulation of the stress response system, including the hypothalamic-pituitary-adrenal (HPA) axis. The International Affective Digitized Sounds-2 (IADS) is widely used in the study of emotions and neuropsychological research. Therefore, in this study, the effects of gum-chewing on physiological and psychological (including PFC activity measured by NIRS) responses to a negative stimulus selected from the IADS were measured and analyzed. The study design was approved by the Ethics Committee of Tokyo Dental College (No. 436). We studied 11 normal adults using: cerebral blood oxygenation in the right medial PFC by multi-channel NIRS; alpha wave intensity by EEG; autonomic nervous function by heart rate; and emotional conditions by the State-Trait Anxiety Inventory (STAI) test and the 100-mm visual analogue scale (VAS). Auditory stimuli selected were fewer than 3.00 in Pleasure value. Sounds were recorded in 3 s and reproduced at random using software. Every task session was designed in a block manner; seven rests: Brown Noise (30 s) and six task blocks: auditory stimuli or auditory stimuli with gum-chewing (30 s). During the test, the participants' eyes were closed. Paired Student's t-test was used for the comparison (P<0.05). Gum-chewing showed a significantly greater activation in the PFC, alpha wave appearance rate and HR. Gum-chewing also showed a significantly higher VAS score and a smaller STAI level indicating 'pleasant'. Gum-chewing affected physiological and psychological responses including PFC activity. This PFC activation change might influence the HPA axis and ANS activities. In summary, within the limitations of this study, the findings suggest that gum-chewing reduced stress-related responses. Gum-chewing might have a possible effect on stress coping.

Papulonecrotic tuberculid-like eruptions after Bacille Calmette-Guerin vaccination.

One of the specific skin lesions occurring after Bacille Calmette-Guerin (BCG) vaccination is generalized tuberculid-like eruptions, which occur rarely, but have a tendency to heal spontaneously. Their pathogenesis and relationship to "true" tuberculids are poorly understood. This report presents a case of a 6-month-old girl who developed generalized papulonecrotic tuberculid-like eruptions after BCG vaccination. The skin lesions healed spontaneously in 3 months. Culture of blood, gastric juice and reverse transcription polymerase chain reaction (RT-PCR) of papulonecrotic skin biopsies were all negative for Mycobacterium tuberculosis. Histopathology of papulonecrotic eruptions revealed marked epidermal necrosis, perivascular lymphocytic infiltrates and epidermotropic infiltration of lymphocytes showing markers of CD3(+) lymphocytes (90-95% of all infiltrating cells), CD4(+) (40-50%), CD8(+) (40-50%), and CD45RO(+) (70%). In contrast, the BCG vaccination site revealed intradermal granuloma with epithelioid cells, occasional giant cells and infiltration of lymphocytes consisting of CD3(+) (60-70%), CD4(+) (40-50%), CD8(+) (30-40%), CD45RO(+) (40%), CD79a(+) (30-40%), and CD20(+) (20-30%). Our patient did not reveal any signs indicative of tuberculosis. Papulonecrotic lesions were therefore called papulonecrotic tuberculid-like eruptions, rather than tuberculids, that occurred after BCG vaccination and appeared to derive from a hypersensitive reaction mediated by immune lymphocytic infiltration.

[Persistent müllerian duct Syndrome in brothers].

Persistent Müllerian duct syndrome is associated with cryptorchidism and transverse testicular ectopia. Such gonads are at an increased risk of malignant transformation. Furthermore, most patients have azoospermia. Here in we report about two brothers with persistent Müllerian duct syndrome. The diagnosis was made during surgical operation for testicular cancer in younger brother. In the other one, persistent Müllerian duct syndrome was diagnosed during examination for infertility.